1. Field of the Invention
The present invention relates to the field of improving the engraftment of hematopoietic stem and progenitor cells in human recipients to treat disease. The invention also relates to a method for decreasing radiation or chemotherapy for hematopoietic pluripotent cell engraftment.
2. Background Art
The practice of bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) involves placing a suspension of donor hematopoietic pluripotent cells (HPCs) into the blood stream of the recipient. HPC transplantations are currently performed with a recipient pre-conditioning regimen of high dosage radiation and/or chemotherapy. The goal of these treatments is to create an environment in the recipient in which the donor""s HPCs can successfully engraft by homing into the recipient""s bone marrow to further undergo hematopoiesis. There may be several objectives for the use of such pre-conditioning regimens, including eliminating cells underlying diseases such as leukemia, or lymphoma, or serving an immunosuppressive function to mitigate graft rejection in the treatment of non-cancerous diseases. Conditioning regimens overall have the desirable effect of eradicating endogenous HPCs to make available more homing sites for transplanted HPCs to successfully engraft. It is believed that current radiation treatments allow homing and engraftment of transplanted stem cells by directly damaging or depleting the recipient""s own stem cells, other hematopoietic regulatory cells, bone marrow stroma, and/or the microcirculatory system. Tavassoli, M., xe2x80x9cThe role of conditioning regimens in homing of transplanted hemopoietic cell,xe2x80x9d Bone Marrow Transplantation, 10:15-17 (1992).
In clinical practice, radiation has been used primarily in high doses to eliminate cells underlying cancerous diseases and to immunosuppress graft rejection. Currently, patients are irradiated with approximately 500 to 1600 cGy at single doses or in fractions. However, the use of radiation can have lethal toxic effects in the recipient, due to the depletion of mature functional blood cells and damage to other organ systems. Therefore, non-myeloablative pre-transplantation regimens, which both minimize radiation effects and attain effective levels of engraftment, are very desirable.
The present invention provides a method of engrafling donor mammalian hematopoietic pluripotent cells in a mammalian recipient using a decreased amount of radiation, comprising: a. administering to the recipient at least one dosage of a hematopoietic growth factor; b. subjecting the recipient to a low dosage of radiation; and, c. transplanting the donor hematopoietic pluripotent cells into the recipient, thereby engrafting the donor mammalian hematopoietic pluripotent cells in the mammalian recipient using a decreased amount of radiation.
The invention also provides a method of engrafting donor mammalian hematopoietic pluripotent cells in a mammalian recipient using a decreased amount of radiomimetic compound, comprising: a. administering to the recipient at least one dosage of a hematopoietic growth factor; b. subjecting the recipient to a low dosage of radiomimetic compound; and, c. transplanting the hematopoietic pluripotent cells into the recipient, thereby engrafling the donor mammalian hematopoietic pluripotent cells in the mammalian recipient using a decreased amount of radio-mimetic compound.